Alcohol amplifies the association between common variants at<i>PRSS1–PRSS2</i>locus and chronic pancreatitis in a dose-dependent manner

Wang, Yuan‐Chen; Mao, Xiaotong; Yu, Dong; Mao, Shenghan; Li, Zhao‐Shen; Zou, Wenbin; Liao, Zhuan

doi:10.1136/gutjnl-2021-326670

Cited by 10 publications

(9 citation statements)

References 10 publications

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“…The effects of smoking on AAP and ACP were partially attenuated after adjusting for alcohol consumption, suggesting that this association is not robust enough in alcohol-induced pancreatitis. Alcohol exposure contributes to the initiation and progression of pancreatitis and amplifies the association between genetic risk factors and CP in a dose-dependent manner ( 41 ). The outcomes in the current study verify the causal associations between alcohol consumption and CP, AAP and ACP.…”

Section: Discussionmentioning

confidence: 99%

Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study

Mao

Mao²,

Sun³

et al. 2023

Front. Immunol.

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BackgroundThe pathogenesis of pancreatitis involves diverse environmental risk factors, some of which have not yet been clearly elucidated. This study systematically investigated the causal effects of genetically predicted modifiable risk factors on pancreatitis using the Mendelian randomization (MR) approach.MethodsGenetic variants associated with 30 exposure factors were obtained from genome-wide association studies. Summary-level statistical data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were obtained from FinnGen consortia. Univariable and multivariable MR analyses were performed to identify causal risk factors for pancreatitis.ResultsGenetic predisposition to smoking (OR = 1.314, P = 0.021), cholelithiasis (OR = 1.365, P = 1.307E-19) and inflammatory bowel disease (IBD) (OR = 1.063, P = 0.008) as well as higher triglycerides (OR = 1.189, P = 0.016), body mass index (BMI) (OR = 1.335, P = 3.077E-04), whole body fat mass (OR = 1.291, P = 0.004) and waist circumference (OR = 1.466, P = 0.011) were associated with increased risk of AP. The effect of obesity traits on AP was attenuated after correcting for cholelithiasis. Genetically-driven smoking (OR = 1.595, P = 0.005), alcohol consumption (OR = 3.142, P = 0.020), cholelithiasis (OR = 1.180, P = 0.001), autoimmune diseases (OR = 1.123, P = 0.008), IBD (OR = 1.066, P = 0.042), type 2 diabetes (OR = 1.121, P = 0.029), and higher serum calcium (OR = 1.933, P = 0.018), triglycerides (OR = 1.222, P = 0.021) and waist-to-hip ratio (OR = 1.632, P = 0.023) increased the risk of CP. Cholelithiasis, triglycerides and the waist-to-hip ratio remained significant predictors in the multivariable MR. Genetically predicted alcohol drinking was associated with increased risk of AAP (OR = 15.045, P = 0.001) and ACP (OR = 6.042, P = 0.014). After adjustment of alcohol drinking, genetic liability to IBD had a similar significant causal effect on AAP (OR = 1.137, P = 0.049), while testosterone (OR = 0.270, P = 0.002) a triglyceride (OR = 1.610, P = 0.001) and hip circumference (OR = 0.648, P = 0.040) were significantly associated with ACP. Genetically predicted higher education and household income levels could lower the risk of pancreatitis.ConclusionsThis MR study provides evidence of complex causal associations between modifiable risk factors and pancreatitis. These findings provide new insights into potential therapeutic and prevention strategies.

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Section: Discussionmentioning

confidence: 99%

Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study

Mao

Mao²,

Sun³

et al. 2023

Front. Immunol.

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“…Finally, alcoholism is also a cause of irreversible chronic pancreatitis. [28][29][30][31][32] In an attempt to resolve some of the controversies in the literature with regard to the relationship between alcoholism and arteriosclerosis, in the present study, we aimed to characterize the relationship between severe chronic alcoholism and hepatic arterial wall disorders in humans.…”

Section: Introductionmentioning

confidence: 99%

Hepatic artery disorders associated with alcoholism

et al. 2023

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Objective We aimed to characterize the relationship between severe chronic alcoholism and hepatic arterial wall disorders in humans. Methods We obtained hepatic arteries from 165 patients undergoing liver transplantation who were placed into two etiological groups: an Alcoholism group and a Non-alcoholism group. We compared the age, sex, lipid profile, and histologic characteristics of the hepatic arteries (normal, reduction in luminal diameter of ≤10%, or atherosclerosis) of the participants in the two groups using multifactor analyses. Results The Alcoholism group comprised 58 men and 40 women and the Non-alcoholism group comprised 63 men and 4 women. The mean ages of the groups were 52.5 ± 9.6 years and 44.2 ± 13.8 years, respectively. There were no circulating lipid abnormalities in any of the participants. In women, arterial disorders were found at a younger age than in men. Hepatic arterial disorders were more frequent in the non-alcoholic participants, and women with alcoholism showed less arterial narrowing. Conclusion The heavy consumption of alcoholic beverages is associated with a lower incidence of atherosclerosis of the hepatic artery in humans.

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“…We read with great interest articles by Wang et al 1 and Hegyi et al , 2 in which the authors reported that alcohol increased the risk of hereditary susceptibility to chronic pancreatitis. These results indicated an interaction effect between environmental and genetic risk factors on the development of pancreatitis.…”

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“…High amounts of ethanol alone may be insufficient to induce clinical AP and is not sufficient to induce murine experimental AP. 7 A genetic predisposition or a susceptible precondition may be required, 1 2 8 9 if not the presence of a cofactor, as in murine fatty acid ethyl ester AP induced by ethanol with palmitoleic or palmitic acid. 7 10 Obesity is an alternative, which our model suggests may be targeted by ATGL inhibition.…”

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confidence: 99%

Alcohol predisposes obese mice to acute pancreatitis via adipose triglyceride lipase-dependent visceral adipocyte lipolysis

Yang

Yao

Dai

et al. 2022

Gut

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Alcohol amplifies the association between common variants atPRSS1–PRSS2locus and chronic pancreatitis in a dose-dependent manner

Cited by 10 publications

References 10 publications

Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study

Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study

Hepatic artery disorders associated with alcoholism

Alcohol predisposes obese mice to acute pancreatitis via adipose triglyceride lipase-dependent visceral adipocyte lipolysis

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